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Transplant immunology

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https://www.readbyqxmd.com/read/28433740/xenotransplantation-of-layer-by-layer-encapsulated-non-human-primate-islets-with-a-specified-immunosuppressive-drug-protocol
#1
Muhammad R Haque, Jiwoong Kim, Hyojun Park, Han Sin Lee, Kyo Won Lee, Taslim A Al-Hilal, Jee-Heon Jeong, Cheol-Hee Ahn, Doo Sung Lee, Sung Joo Kim, Youngro Byun
Islet transplantation is as effective as but also less immunogenic than pancreas transplantation for the treatment of type 1 diabetes mellitus. However, as the complete elimination of immunogenicity still remains a major obstacle in islet transplantation, layer-by-layer encapsulation (LbL) of pancreatic islets using biocompatible polymers offers a rational approach to reducing host immune response towards transplanted islets. We investigated the effect of LbL of non-human primate (NHP) islets on reducing immunogenicity as a preclinical model since NHPs have close phylogenetic and immunological relationship with human...
April 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28431262/immunologic-approaches-for-the-treatment-of-multiple-myeloma
#2
REVIEW
Leo Rasche, Niels Weinhold, Gareth J Morgan, Frits van Rhee, Faith E Davies
The FDA approval of two monoclonal antibodies in 2015has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, 'off-target' immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies...
April 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28427861/divergent-function-of-programmed-death-ligand-1-in-donor-tissue-versus-recipient-immune-system-in-a-murine-model-of-bronchiolitis-obliterans
#3
Katharina Schütte-Nütgen, Olaf Boenisch, Hakima Harrach, Alicia Casey, Indira Guleria, Nader Najafian, Mohamed H Sayegh, Craig J Gerard, Meera Subramaniam
Costimulatory molecules, such as the programmed death ligand (PD-L1), might exert differential effects on T-cell function, depending on the clinical setting and/or immunological environment. Given the impact of T cells on bronchiolitis obliterans (BO) in lung transplantation, we used an established tracheal transplant model inducing BO-like lesions to investigate the impact of PD-L1 on alloimmune responses and histopathological outcome in BO. In contrast to other transplant models in which PD-L1 generally shows protective functions, we demonstrated that PD-L1 has divergent effects depending on its location in donor versus recipient tissue...
April 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28417321/adjuvanted-as03-a-h1n1-2009-pandemic-influenza-vaccines-and-solid-organ-transplant-rejection-systematic-signal-evaluation-and-lessons-learnt
#4
Gaël Dos Santos, Harry A Seifert, Vincent Bauchau, Vivek Shinde, Dominique M Barbeau, Catherine Cohet
INTRODUCTION: We investigated a signal of solid organ transplant (SOT) rejection after immunisation with (AS03) A/H1N1 2009 pandemic influenza vaccines. METHODS: Potential immunological mechanisms were reviewed and quantitative analyses were conducted. The feasibility of pharmacoepidemiological studies was explored. RESULTS: Overall results, including data from a pharmacoepidemiological study, support the safety of adjuvanted (AS03) pandemic influenza vaccination in SOT recipients...
April 17, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28413492/immunogenicity-of-insulin-producing-cells-derived-from-human-umbilical-cord-mesenchymal-stem-cells
#5
Xiao-Fei Yang, Tao Chen, Li-Wei Ren, Lu Yang, Hui Qi, Fu-Rong Li
Mesenchymal stem cells (MSCs) have been considered as hypo-immunogenic and immunosuppressive. However, a thorough understanding of the immunological properties after MSC differentiation in vitro and in vivo has not been reached. We asked whether it would be immunogenic after differentiation or influenced by the immune microenvironment after transplantation. In different disease models, the immunological changes of MSCs after differentiation greatly varied, with contradicting results. In order to clarify this, we used a modified four-step induction method to induce human umbilical cord MSCs (hUCMSCs) to differentiate into insulin-producing cells (IPCs), and investigate the immunological changes after differentiation and immune reactions after transplantation into diabetic mice...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28412300/mechanisms-of-retinal-damage-after-ocular-alkali-burns
#6
Eleftherios I Paschalis, Chengxin Zhou, Fengyang Lei, Nathan Scott, Vassiliki Kapoulea, Marie-Claude Robert, Demetrios Vavvas, Reza Dana, James Chodosh, Claes H Dohlman
Alkali burns to the eye constitute a leading cause of worldwide blindness. In recent case series, corneal transplantation revealed unexpected damage to the retina and optic nerve in chemically burned eyes. We investigated the physical, biochemical, and immunological components of retinal injury after alkali burn and explored a novel neuroprotective regimen suitable for prompt administration in emergency departments. Thus, in vivo pH, oxygen, and oxidation reduction measurements were performed in the anterior and posterior segment of mouse and rabbit eyes using implantable microsensors...
April 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28408734/mycophenolate-mofetil-and-pulmonary-fibrosis-after-kidney-transplantation-a-case-report
#7
Kazuhiro Takahashi, Pauline Go, Chad H Stone, Mohamed Safwan, Krishna G Putchakayala, William J Kane, Lauren E Malinzak, Dean Y Kim, Jason E Denny
BACKGROUND Mycophenolate mofetil (MMF) induced lung disease has been described in only a few isolated reports. We report a case of fatal respiratory failure associated with MMF after kidney transplantation. CASE REPORT A 50-year-old Hispanic male with a history of end-stage renal disease secondary to hypertension underwent deceased donor kidney transplantation. His preoperative evaluations were normal except for a chest x-ray which showed bilateral interstitial opacities. Tacrolimus and MMF were started on the day of surgery...
April 14, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28403127/a-randomized-controlled-clinical-trial-comparing-belatacept-with-tacrolimus-after-de-novo-kidney-transplantation
#8
Gretchen de Graav, Carla C Baan, Marian C Clahsen-van Groningen, Rens Kraaijeveld, Marjolein Dieterich, Wenda Verschoor, Jan H von der Thusen, Dave L Roelen, Monique Cadogan, Jacqueline van de Wetering, Joost van Rosmalen, Wilem Weimar, Dennis A Hesselink
BACKGROUND: Belatacept, an inhibitor of the CD28-CD80/86 co-stimulatory pathway, allows for calcineurin-inhibitor free immunosuppressive therapy in kidney transplantation but is associated with a higher acute rejection risk than ciclosporin. Thus, no biomarker for belatacept-resistant rejection has been validated. In this randomized controlled trial, acute rejection-rate was compared between belatacept- and tacrolimus-treated patients and immunological biomarkers for acute rejection were investigated...
April 11, 2017: Transplantation
https://www.readbyqxmd.com/read/28402253/immunoregulatory-role-of-b-lymphocytes-in-alloresponse-to-kidney-transplant
#9
Tomasz Baran, Maria Boratyńska
B cells are a group of diverse phenotype and function subsets, which can both stimulate and inhibit the immune response to an allograft. They participate in the rejection process by influencing differentiation, proliferation and effector functions of T lymphocytes. B cells injure the graft via the ADCC (antibody-dependent cellular cytotoxicity) reaction and humoral rejection through plasmocyte production of donor-specific antibodies. A converse, suppressive mode of B cells can attribute to the development of tolerance and protect the graft from rejection...
April 12, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28399164/sequential-monitoring-of-lymphocyte-subsets-and-of-t-and-b-cell-neogenesis-indexes-to-identify-time-varying-immunologic-profiles-in-relation-to-graft-versus-host-disease-and-relapse-after-allogeneic-stem-cell-transplantation
#10
Cristina Skert, Simone Perucca, Marco Chiarini, Viviana Giustini, Alessandra Sottini, Claudia Ghidini, Stefano Martellos, Federica Cattina, Benedetta Rambaldi, Valeria Cancelli, Michele Malagola, Alessandro Turra, Nicola Polverelli, Simona Bernardi, Luisa Imberti, Domenico Russo
T and B lymphocyte subsets have been not univocally associated to Graft-versus-host disease (GVHD) and relapse of hematological malignancies after stem cell transplantation (SCT). Their sequential assessment together with B and T cell neogenesis indexes has been not thoroughly analysed in relation to these changing and interrelated immunologic/clinic events yet. Lymphocyte subsets in peripheral blood (PB) and B and T cell neogenesis indexes were analysed together at different time points in a prospective study of 50 patients...
2017: PloS One
https://www.readbyqxmd.com/read/28399040/a-new-enzyme-linked-immunosorbent-assay-elisa-for-a-total-anti-t-lymphocyte-globulin-determination-development-analytical-validation-and-clinical-application
#11
M Montagna, G La Nasa, M E Bernardo, E Piras, M A Avanzini, M Regazzi, F Locatelli
BACKGROUND: Anti-T lymphocyte globulin (ATLG) modulates the alloreactivity of T lymphocytes, reducing the risk of immunological post-transplant complications, in particular rejection and graft-versus-host disease (GvHD), after allogeneic hematopoietic stem cell transplantation (HSCT).We developed and validated a new enzyme-linked immunosorbent assay (ELISA) method to measure serum levels of total ATLG and evaluate the pharmacokinetics (PK) of the drug in children with β-Thalassemia, receiving allogeneic HSCT...
April 7, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28395110/murine-models-of-transplantation-tolerance-through-mixed-chimerism-advances-and-roadblocks
#12
REVIEW
Benedikt Mahr, Thomas Wekerle
Organ transplantation is the treatment of choice for patients with end-stage organ failure but chronic immunosuppression is taking its toll in terms of morbidity and poor efficacy in preventing late graft loss. Therefore a drug-free state would be desirable where the recipient permanently accepts a donor organ while remaining otherwise fully immunologically competent. Mouse studies unveiled mixed chimerism as an effective approach to deliberately induce such donor-specific tolerance and laid the foundation for a series of clinical pilot trials...
April 10, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28392163/current-progress-in-non-viral-rnai-based-delivery-strategies-to-lymphocytes
#13
REVIEW
Shoshy Mizrahy, Inbal Hazan-Halevy, Niels Dammes, Dalit Landesman-Milo, Dan Peer
RNAi-based therapy holds great promise, as it can be utilized for the treatment of multiple conditions in an accurate manner via sequence-specific manipulation of gene expression. To date, RNAi therapeutics have advanced into clinical trials for liver diseases and solid tumors; however, delivery of RNAi to leukocytes in general and to lymphocytes in particular remains a challenge. Lymphocytes are notoriously hard to transduce with RNAi payloads and are disseminated throughout the body, often located in deep tissues; therefore, developing an efficient systemic delivery system directed to lymphocytes is not a trivial task...
April 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28385038/review-of-mechanical-processing-and-immunologic-factors-associated-with-outcomes-of-fresh-osteochondral-allograft-transplantation-of-the-talus
#14
Chikezie N Okeagu, Erin A Baker, Nicholas A Barreras, Zachary M Vaupel, Paul T Fortin, Kevin C Baker
Osteochondral lesions of the talus (OLTs) are an increasingly implicated cause of ankle pain and instability. Several treatment methods exist with varying clinical outcomes. Due in part to successful osteochondral allografting (OCA) in other joints, such as the knee and shoulder, OCA has gained popularity as a treatment option, especially in the setting of large lesions. The clinical outcomes of talar OCA have been inconsistent relative to the positive results observed in other joints. Current literature regarding OCA failure focuses mainly on 3 factors: the effect of graft storage conditions on chondrocyte viability, graft/lesion size, and operative technique...
April 1, 2017: Foot & Ankle International
https://www.readbyqxmd.com/read/28384413/comparative-effectiveness-of-tacrolimus-based-steroid-sparing-versus-steroid-maintenance-regimens-in-kidney-transplantation-results-from-discrete-event-simulation
#15
Vibha C A Desai, Yann Ferrand, Teresa M Cavanaugh, Christina M L Kelton, J Jaime Caro, Jens Goebel, Pamela C Heaton
BACKGROUND: Corticosteroids used as immunosuppressants to prevent acute rejection (AR) and graft loss (GL) following kidney transplantation are associated with serious cardiovascular and other adverse events. Evidence from short-term randomized controlled trials suggests that many patients on a tacrolimus-based immunosuppressant regimen can withdraw from steroids without increased AR or GL risk. OBJECTIVES: To measure the long-term tradeoff between GL and adverse events for a heterogeneous-risk population and determine the optimal timing of steroid withdrawal...
April 1, 2017: Medical Decision Making: An International Journal of the Society for Medical Decision Making
https://www.readbyqxmd.com/read/28379858/keratolimbal-allograft
#16
Albert Y Cheung, Edward J Holland
PURPOSE OF REVIEW: Keratolimbal allograft (KLAL) transplants limbal tissue attached to a corneoscleral carrier from a cadaveric donor to deliver a large number of stem cells to the recipient. The present article will provide a review of KLAL focusing on the recent literature. RECENT FINDINGS: Recent findings pertain to tissue selection, immunosuppression and adverse event profiles, and postoperative complications (particularly related to immunologic rejection). SUMMARY: KLAL permits the treatment of limbal stem cell deficiency eyes when there is no available living-related or autograft tissue with minimal risk of irreversible toxicity from modern systemic immunosuppression...
April 4, 2017: Current Opinion in Ophthalmology
https://www.readbyqxmd.com/read/28379044/advances-in-umbilical-cord-blood-cell-therapy-the-present-and-the-future
#17
Sofia Berglund, Isabelle Magalhaes, Ahmed Gaballa, Bruno Vanherberghen, Michael Uhlin
Umbilical cord blood (UCB), previously seen as medical waste, is increasingly recognized as a valuable source of cells for therapeutic use. The best-known application is in hematopoietic stem cell transplantation (HSCT), where UCB has become an increasingly important graft source in the 28 years since the first umbilical cord blood transplantation (UCBT) was performed. Recently, UCB has been increasingly investigated as a putative source for adoptive cell therapy. Areas covered: This review covers the advances in umbilical cord blood transplantation (UCBT) to overcome the limitation regarding cellular dose, immunological naivety and additional cell doses such as DLI...
April 5, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28373413/acute-graft-versus-host-disease-a-comprehensive-review
#18
REVIEW
Samah Nassereddine, Hind Rafei, Ehab Elbahesh, Imad Tabbara
Acute graft versus host disease (aGVHD) remains the second leading cause of death following allogeneic hematopoietic stem cell transplant (AHSCT). Over the last five years, the progress in understanding the pathophysiology of this immune based-process helped redefine graft versus host reaction and opened new possibilities for novel preventive and therapeutic approaches. The evolution in the field of immunology widened the horizons for hematopoietic stem cell transplant leading to the availability of different stem cell sources for potential graft and incorporation of novel conditioning regimens...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28372951/disturbances-in-iron-homeostasis-result-in-accelerated-rejection-after-experimental-heart-transplantation
#19
Thomas Resch, Muhammad Imtiaz Ashraf, Paul Viktor Ritschl, Susanne Ebner, Cornelia Fabritius, Andrea Brunner, Georg Schäfer, Heinz Regele, Julia Günther, Günter Weiss, Katja Kotsch
BACKGROUND: Clinical data suggest that iron disturbances deleteriously affect graft survival after heart transplantation (HTx), but immunological mechanisms underlying this phenomenon have not yet been elucidated. METHODS: To identify the mechanistic influence of iron in a murine model of HTx, fully allogeneic BALB/c donor organs were transplanted into iron-overloaded or iron-deficient C57BL/6 mice, and recipients were analyzed for functional and immunological parameters...
March 7, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28371374/vitamin-a-deficiency-in-chronic-cholestatic-liver-disease-is-vitamin-a-therapy-beneficial
#20
Cora Freund, Daniel Nils Gotthardt
Chronic cholestatic diseases are progressive diseases of the biliary tract that cause hepatic fibrosis and ultimately lead to liver failure. Liver transplantation is the sole curative option currently available, and because of high morbidity and mortality rates of these diseases, new therapeutic approaches are needed. Vitamin A is a nutrient essential for health as it regulates many processes, including epithelial growth and immunological processes. Vitamin A is primarily stored in hepatic stellate cells, and during liver injury, through an unknown mechanism, these cells lose vitamin A and convert into collagen-producing myofibroblasts, which contributes to hepatic fibrosis...
March 29, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
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